Non-Hodgkin lymphomas are a heterogenous group of hematologic malignancies derived in more than 90% from B-lymphocytes, one subtype of white blood cells. B-cells are part of adaptive immune system and one of their main functions is to recognize antigens and differentiate into plasmatic cells to produce antibodies. Hallmark molecule of B-cells is B-cell receptor (BCR), which is specifically responsible for antigen binding and recognition. Majority of B-cell derived malignancies retain surface expression of BCR, which is actively signaling and supports growth and survival of tumor cells.
Similarly, as is heterogonous group of lymphomas, differences exist also in types of signaling it provides. In some lymphomas, BCR signals through “chronic active” type of BCR signaling that resembles normal signaling after antigen binding, in other lymphomas, BCR signaling resembles “tonic” type of signaling that normally provides basic signal necessary for survival of mature B-cells. However, many details and differences in BCR signal initiation and its transmission to individual signal mediators are not fully characterized. Inhibition of BCR signaling and its related signal mediators is also one of novel strategies of lymphoma treatment, but more information is needed to identify novel therapeutic targets or personalize use of existing inhibitors.
Latest developments in technology and related research resulted in unprecedented advancement in our understanding of mechanisms leading to lymphomagenesis, however, many mechanisms of aberrant signaling, metabolic changes, transcription regulation, or interactions of tumor cells with tumor microenvironment are still not clear.
Using advanced methods for targeted genomic modifications, protein-protein interactions detection, high-resolution microscopy, or intracellular biosensors, the general aim of our group is to address missing information about cellular processes critical for lymphoma development and tumor cell growth with contribution to basic knowledge of these processes in general.
- Describe differences and mechanisms of B-cell receptor signal initiation, its localization and interaction with signal mediators, and mechanisms of PI3K/AKT pathway activation in different types lymphomas and states of BCR signaling.
- Identify biomarkers to personalize use of BCR signaling inhibitors.
- Investigate novel candidates for gene expression dysregulation in lymphoma.
- Investigate relationship of driver lymphoma characteristics on development of tumor microenvironment using lymphoma mouse models.
Further information can be found also at https://havranek-lab.lf1.cuni.cz/about-us